Quinoline based thiosemicarbazones as colorimetric chemosensors for fluoride and cyanide ions and DFT studies

High toxicity and extensive accessibility of fluoride and cyanide ions in diverse environmental media encouraged attention for scheming well-organized probes for their detection. Keeping in mind we have designed and synthesized thiosemicarbazone-based chemosensors RB-1, RB-2 and RB-3 for the detection of fluoride and cyanide ions. The structural elucidation of the synthesized chemosensors is done by employing different analytical techniques including nuclear magnetic resonance and electronic absorption specrtoscopies. Admirable detection limit, binding constant and fast response time (2 s) to F− and CN− ions enlarged the applications of these chemosensors. Additional confirmation of the sensing ability of these chemosensors is derived from DFT and TDDFT calculations with M06/6-311G(d,p) method by performing FMO, UV–Vis, QTAIM and global reactivity parameters elucidation. Overall results point out that investigated chemosensors are suitable candidates for sensing the F− ions. These chemosensors were successfully applied to detect F− ions in a commercial toothpaste sample.


High toxicity and extensive accessibility of fluoride and cyanide ions in diverse environmental media encouraged attention for scheming well-organized probes for their detection. Keeping in mind we have designed and synthesized thiosemicarbazone-based chemosensors RB-1, RB-2 and RB-3 for the detection of fluoride and cyanide ions. The structural elucidation of the synthesized chemosensors is done by employing different analytical techniques including nuclear magnetic resonance and electronic absorption specrtoscopies. Admirable detection limit, binding constant and fast response time (2 s) to F − and CN − ions enlarged the applications of these chemosensors. Additional confirmation of the sensing ability of these chemosensors is derived from DFT and TDDFT calculations with M06/6-311G(d,p) method by performing FMO, UV-Vis, QTAIM and global reactivity parameters elucidation.
Overall results point out that investigated chemosensors are suitable candidates for sensing the F − ions. These chemosensors were successfully applied to detect F − ions in a commercial toothpaste sample.
In supramolecular chemistry, selective and sensitive detection of anions have attracted a great attention due to their biomedical, environmental and chemical applications [1][2][3][4][5] . Among the numerous anions CN − and F − are immensely harmful to environment and human health 6 . The fluoride is the smallest and most electronegative ion that promotes healthy bone growth and avoids dental cavities due to which it is considered as a micronutrient 7 . The F − ions are commonly present in toothpaste, pharmaceutical agents and drinking water due to their significant role in avoiding dental caries and treatment of osteoporosis 8 . The F − ions are also used for the separation of radioactive and non-radioactive substances in nuclear industry 9 . Apart from its biological activity, the F − ions are also used as potential catalysts in synthesis and is identified as a strong Lewis's base 10 . In addition, the F − ions have also various industrial application mainly in steel and aluminum industries 11 . The rate of absorption of the F − ions are fast as compared to excretion 12 . The World Health Organization (WHO) has set the extreme limit of F − ions (1.5 mg L −1 ) for human health 13 . The high intake of the F − ions cause fluorosis which is supplemented with set of diseases such as tooth mottling, metabolic disturbances and neurotoxicity 14 . In molecular and cell biology, a greater concentration of NaF also affects the cell signaling processes and thus causes apoptosis 15 . Besides this, it was also expected that the F − ions with higher concentration cause mitochondrial disorder and promote mitochondrial oxidative stress 16 . Similarly, the CN − ions are widely known as toxic and extremely effective species to human health. Though, the CN − ions are extensively used in industrial developments, such as artificial plastic and gum industry, production of pharmaceutical, gold-silver mining, metallurgy and X-ray film recovery 17,18 . In nature, various food and plants also contain CN − ions 17 . In chemical industry, the CN − salt (1.5 million ton/ year) are also involved in synthesis of nitriles, nylon, and acrylic polymer 19 Table 1.

Real-life applications.
To check the response of these chemosensors to F − ions in real sample, we used commercially available tooth -paste as a source of F − ions. The toothpaste sample for analysis was prepared by dissolving 50 mg of commercially available tooth-paste (Sensodyne) in 3 mL CH 3 CN with sonication followed by centrifugation and filtration. When the filtrate of toothpaste sample (50 µM) was added to chemosensors solutions (10 µM) the bands at 385 were reduced with the emergence of new bands at 445, 450 and 450 nm for RB-1, RB-2 and RB-3 respectively (Fig. 4). The color of solutions was also changed from colorless to yellowish.    50 . The solution of DNA was titrated against a fixed concentration of chemosensors (1 mM) and absorption measurement were taken at regular intervals as showen in (Fig. 5). The absorption data showed significant hypochromic shifts by the addition of SS-DNA that we speculate is caused by intercalative mode of binding though. π-stacking between SS-DNA and title compounds 51

Reversibility of reaction.
Methanol is a good proton donor as compared to N-H group of chemosensors (RB-1, RB-2 and RB-3) thus reversible reaction with the addition of methanol was expected as reported somewhere else 52,53 . When 0.1 ml of methanol was added to solutions of chemosensors and fluoride ions, yellow color of the solution was disappeard which indicates the re-protonation of chemosensors (Fig. 6). And the electronic absorption spectra were also reversed to original bands of chemosensors at 350 nm and 285 nm. This observation suggests thst methanol interaction between chemosensor and F − ions can be reversed by the addition of a stronger proton donor.
Sensing mechanism. 1 HNMR and IR spectroscopy [S.I. 29] were engaged to confirm the proof of the proposed mechanism of chemosensor (RB-1) interaction with F − ions. Tetra-n-butylammonium fluoride (TBAF) was used as source of Fˉ ions and it was slowely added to chemosensor RB-1 solution in DMSO-d 6 . The 1 H-NMR spectrum of (RB-1) endorses presence of NH protons as sharp singlets at δ 12.30 and δ10.35 ppm. The vanishing of NH protons when F − ions were added indicates that F − ions abstract NH proton (Fig. 7). The proposed sensing mechanism 54 is illustrated in (Scheme 2).

Theoretical study
The optimized geometries of RB-1, RB-2 and RB-3 chemosensors in the absence and presence of F − ions are presented in (Fig. 8).   Among free chemosensors, the lowest energy gap value (3.829 eV) is measured in RB-3, while highest energy gap is marked as 3.904 eV in RB-2. The backbone of RB-1, RB-2, RB-3 contains Cl, S, and N atoms at the same position. The only difference is the presence of F, Cl and OCH 3 units on the terminal benzene ring respectively. These units cause the difference in the energy gap values of free chemosensors. The lowest E g value in RB-3 might be attributed to the presence of moderately activating OCH 3 groups which form a push-pull configuration with weakly deactivating Cl in RB-3. The highest energy gap in RB-2 is occurred owing to the presence of same weakly deactivating Cl atoms in backbone as well as on terminal benzene ring (Fig. 9).
The outcomes summarized in Table 2
Global softness and hardness are crucial GRPs that are used to describe the chemical nature of the molecules under investigation. It can be seen from Table 3 results that softness values in free chemosensors are larger compared to complexed chemosensors. This implies that the stability of chemosensors is increased in the presence of F − ions. Similar results are marked in case of hardness values which are found in the range of 1.914-1.952 in the absence of ions and 2.049-2.060 in the presence of ions. Global hardness results also favor the stance that chemosensors RB-1, RB-2, RB-3 upon addition of fluoride ions convert into kinetically stable, hard and less reactive chemosensors. Larger IP values of complexed chemosensors RB-1 + F − ions, RB-2 + F − ions, RB-3 + F − ions as compared to free RB-1, RB-2, RB-3 chemosensors tell the same story of more stability, less reactivity and their hard nature. From electronegativity and chemical potential results, it can be inferred that increased values of X and decreased values of μ in RB-1 + F − ions, RB-2 + F − ions, RB-3 + F − ions than RB-1, RB-2, RB-3 is due to the formation of H-F bonds. Overall, the presence of stability, hard nature, and less reactivity of RB-1 + F − ions, QT-AIM analysis. QT-AIM study was achieved to assess the intra-and intermolecular non-covalent interactions like hydrogen bonds (HBs) via Theory of Atoms in Molecules 60-62 for the entitled compounds such as RB-1, RB-3 and RB-1, respectively (Fig. 10). Non-covalent intermolecular interactions gained a lot of attention due to their performance in the maintenance of molecular arrangement. They could manage the intermolecular aggregation processes in terms of the polarity and nature of the involved species 63 . The non-covalent interactions (NCI) phenomenon is accomplished by calculating real-space regions where non-covalent interactions are necessary and depend altogether on ρ and its gradient 64 65,66 . The AIM analysis showed that the molecules having inter-and intra-molecular interactions are stable and these interactions can be observed by the dashed bond path (BPs) between the atoms (Fig. 10).
For entitled compounds, two different sets of HBs existed; one intra-molecular and the other with solvent interaction. The intra-molecular HB exhibition was found between nitrogen of hydrazine moiety and the hydrogen of the benzene ring, as their ρ values at BCPs were found to be + 0.011203 e/a 3 (N14-H36), and + 0.011622 e/a 3 (N14-H35) and + 0.011540 e/a 3 (N14-H34) for RB-1, RB-2 and RB-3 respectively. The solvent-based HBs were much less strong in comparison to the intra-molecular HBs.

Conclusion
In summary, a series of novel quinoline fluorophore based chemosensors (RB-1, RB-2 and RB-3) for detection of F − and CN − ions were synthesized. When these chemosensors were treated with F − and CN − ions a new absorbance band appeared which can be reinstated to original one by treating with MeOH. Chemosensors presented a very fast comeback to F − ions (2 s) with change in color from colorless to yellow. The red-shifting of absorption maximum values upon sensing the F − ions in RB-1 + F − ions, RB-2 + F − ions, RB-3 + F − ions and changes in spectral properties due to formalization of complex are measured which were also well reflected in experimental calculated spectral analyses of free and